Musings of an oft-bemused former laboratory postdoc

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Shining light

So, is nobody here on this scientific forum acknowledging today’s 25th anniversary of a very important scientific discovery by one of our greatest living scientists? Well, here’s a bit of précised technical detail:

’In 1984, after isolating a short minisatellite comprised of a 33 base-pair sequence tandemly repeated four times from an intron of the human myoglobin gene, Alec Jeffreys and colleagues set about the search for other hypervariable regions, using the myoglobin minisatellite 33 bp sequence as the basis for manufacturing a probe. The single 33 bp element was ligated to form a polymer, which was cloned, generating a 767 bp probe containing 23 repeats of the 33 bp sequence. This probe was used on restriction fragments of human genomic DNA, from three family members (father, mother, daughter), digested with Hae III or Hin fI, two enzymes whose 4 bp recognition sites are absent from the 33 bp repeat. These enzymes usually yield human DNA fragments of 0.3 kb on average; however, the probe hybridised to several fragments in the size range 2 – 6 kb that displayed considerable variation, ie, polymorphism. These fragments also revealed a Mendelian transmission pattern from parents to daughter.

Subsequently, a human genomic DNA library was screened with the same probe. Eight of 40 hybridising clones were randomly selected and sequenced. This revealed that each of these eight clones contained a minisatellite tandem repeat of three to 29 copies. This repeat varied in length from 16 to 64 bp. Probes were then prepared from each of the eight minisatellites and used to screen human DNA from 14 unrelated individuals, at high stringency. Three of these revealed highly polymorphic variation in length due to differing copy number of the repeat. The eight minisatellite sequences were then aligned and compared with the original myoglobin 33 bp repeat sequence, revealing a consensus 15 bp core sequence common to all. Resembling the χ recombination sequence of E. coli, this core is believed to be responsible for generation of polymorphism among minisatellites by unequal exchange. It was, therefore, realised that a probe consisting purely of repeats of this core sequence would be capable of picking out more minisatellites from within the human genome than had so far been discovered. One of the above eight clones, comprising 29 repeats of an almost perfect 16 bp core sequence, provided this probe, which was used to screen the DNA of 54 members of a four generation pedigree. Remarkably, each of these related individuals revealed a different pattern of minisatellite hybridisation with the probe – including the two children of a consanguineous marriage. Transmission of these minisatellites was autosomal and Mendelian, enabling the tracing of these genetic markers through lineages.

It was subsequently shown that, due to its stability, DNA could be isolated from bloodstains several years old – and from semen obtained from vaginal swabs. Thus, the potential for this technique in forensic analysis was realised and it was suitably named ‘DNA fingerprinting.’ It wasn’t long before the first forensic application of DNA fingerprinting, solving the linked murders of two schoolgirls – which occurred just six miles from where this dramatic invention was made.’

The above is dryly excerpted from my Human Genetics module dissertation (entitled ‘History of Human Genetics’), which I produced in 1996 during the final year of my undergraduate degree at the University of Leicester. As a mad keen mature student, I was privileged, not long after the OJ Simpson trial, to attend lectures and tutorials given by Alec Jeffreys, whose work had, for me, added interest, coming as I do from the area of Leicester where occurred those two murders, and had myself contributed a sample to ‘The Blooding’.

That he marked me highly for my dissertation is irrelevant (although mighty pleasing at the time). What is relevant is the impact of his discovery – it contributes to the solving of crimes by the thousands, not to mention numerous other applications. Yet he maintains, quite rightly in my opinion, that innocent people’s data should not be stored on the DNA database.

So come on, nominators for the Nobel Prize in Chemistry; what are you waiting for?